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https://www.readbyqxmd.com/read/27864148/three-pentraxins-c-reactive-protein-serum-amyloid-p-component-and-pentraxin-3-mediate-complement-activation-using-collectin-cl-p1
#1
Nitai Roy, Katsuki Ohtani, Yoshihiko Hidaka, Yoshiro Amano, Yasuyuki Matsuda, Kenichiro Mori, Insu Hwang, Norimitsu Inoue, Nobutaka Wakamiya
BACKGROUND: Pentraxins (PTXs) are a superfamily of multifunctional conserved proteins involved in acute-phase responses. Recently, we have shown that collectin placenta 1 (CL-P1) and C-reactive protein (CRP) mediated complement activation and failed to form terminal complement complex (TCC) in normal serum conditions because of complement factor H inhibition. METHODS: We used CL-P1 expressing CHO/ldlA7 cells to study the interaction with PTXs. Soluble type CL-P1 was used in an ELISA assay for the binding, C3 and TCC deposition experiments...
November 15, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27849512/a-fatal-case-of-invasive-infection-caused-by-w135-neisseria-meningitidis-in-a-vaccinated-french-soldier
#2
Sandrine Duron, Christophe Martinaud, David Lacassagne, Jean-Louis Koeck
We report on the case of fatal "purpura fulminans" caused by Neisseria meningitidis W135 that occurred in a young French soldier vaccinated a few months earlier with the tetravalent conjugate vaccine ACYW135. Biological investigations revealed adequate titers of postvaccination antibodies against serogroups A, C, and W135 and led to the post-mortem diagnosis of a complete C7 complement deficiency. Late complement component deficiency is a well-known risk factor of meningococcal diseases, but usually exposes to recurrent mild infections, whereas severe invasive meningococcal diseases are more likely to occur among properdin-deficient patients...
November 2016: Military Medicine
https://www.readbyqxmd.com/read/27824045/hybrid-mass-spectrometry-approaches-in-glycoprotein-analysis-and-their-usage-in-scoring-biosimilarity
#3
Yang Yang, Fan Liu, Vojtech Franc, Liem Andhyk Halim, Huub Schellekens, Albert J R Heck
Many biopharmaceutical products exhibit extensive structural micro-heterogeneity due to an array of co-occurring post-translational modifications. These modifications often effect the functionality of the product and therefore need to be characterized in detail. Here, we present an integrative approach, combining two advanced mass spectrometry-based methods, high-resolution native mass spectrometry and middle-down proteomics, to analyse this micro-heterogeneity. Taking human erythropoietin and the human plasma properdin as model systems, we demonstrate that this strategy bridges the gap between peptide- and protein-based mass spectrometry platforms, providing the most complete profiling of glycoproteins...
November 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27811836/recommendations-for-use-of-meningococcal-conjugate-vaccines-in-hiv-infected-persons-advisory-committee-on-immunization-practices-2016
#4
Jessica R MacNeil, Lorry G Rubin, Monica Patton, Ismael R Ortega-Sanchez, Stacey W Martin
At its June 2016 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of meningococcal conjugate vaccine (serogroups A, C, W, and Y; including MenACWY-D [Menactra, Sanofi Pasteur] or MenACWY-CRM [Menveo, GlaxoSmithKline]) for persons aged ≥2 months with human immunodeficiency virus (HIV) infection. ACIP has previously recommended routine vaccination of persons aged ≥2 months who have certain medical conditions that increase risk for meningococcal disease (1), including persons who have persistent (e...
November 4, 2016: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/27782331/properdin-a-tightly-regulated-critical-inflammatory-modulator
#5
REVIEW
Adam Z Blatt, Sabina Pathan, Viviana P Ferreira
The complement alternative pathway is a powerful arm of the innate immune system that enhances diverse inflammatory responses in the human host. Key to the effects of the alternative pathway is properdin, a serum glycoprotein that can both initiate and positively regulate alternative pathway activity. Properdin is produced by many different leukocyte subsets and circulates as cyclic oligomers of monomeric subunits. While the formation of non-physiological aggregates in purified properdin preparations and the presence of potential properdin inhibitors in serum have complicated studies of its function, properdin has, regardless, emerged as a key player in various inflammatory disease models...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782329/complement-in-removal-of-the-dead-balancing-inflammation
#6
REVIEW
Myriam Martin, Anna M Blom
Recognition and removal of apoptotic and necrotic cells must be efficient and highly controlled to avoid excessive inflammation and autoimmune responses to self. The complement system, a crucial part of innate immunity, plays an important role in this process. Thus, apoptotic and necrotic cells are recognized by complement initiators such as C1q, mannose binding lectin, ficolins, and properdin. This triggers complement activation and opsonization of cells with fragments of C3b, which enhances phagocytosis and thus ensures silent removal...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27777575/activation-of-human-complement-system-by-dextran-coated-iron-oxide-nanoparticles-is-not-affected-by-dextran-fe-ratio-hydroxyl-modifications-and-crosslinking
#7
Guankui Wang, Fangfang Chen, Nirmal K Banda, V Michael Holers, LinPing Wu, S Moein Moghimi, Dmitri Simberg
While having tremendous potential as therapeutic and imaging tools, the clinical use of engineered nanoparticles has been associated with serious safety concerns. Activation of the complement cascade and the release of proinflammatory factors C3a and C5a may contribute to infusion-related reactions, whereas opsonization with C3 fragments promotes rapid recognition and clearance of nanomaterials by mononuclear phagocytes. We used dextran-coated superparamagnetic iron oxide nanoparticles (SPIO), which are potent activators of the complement system, to study the role of nanoparticle surface chemistry in inciting complement in human serum...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27756886/properdistatin-inhibits-angiogenesis-and-improves-vascular-function-in-human-melanoma-xenografts-with-low-thrombospondin-1-expression
#8
Jon-Vidar Gaustad, Trude G Simonsen, Lise Mari K Andersen, Einar K Rofstad
In this study, the effect of properdistatin, a novel peptide derived from the thrombospondin 1 (TSP-1) domain of properdin, was investigated in three melanoma xenograft models with different TSP-1 expression. The tumors were grown in dorsal window chambers and were treated with 80 mg/kg/day properdistatin or vehicle. Morphological parameters of the tumor vasculature were assessed from high resolution transillumination images. Blood supply time (i.e., the time required for arterial blood to flow from a supplying artery to downstream microvessels) and plasma velocities were assessed from first-pass imaging movies recorded after a bolus of fluorescence-labeled dextran had been administered intravenously...
October 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27573083/recommendations-for-serogroup-b-meningococcal-vaccine-for-persons-10-years-and-older
#9
(no author information available yet)
This policy statement provides recommendations for the prevention of serogroup B meningococcal disease through the use of 2 newly licensed serogroup B meningococcal vaccines: MenB-FHbp (Trumenba; Wyeth Pharmaceuticals, a subsidiary of Pfizer, Philadelphia, PA) and MenB-4C (Bexsero; Novartis Vaccines, Siena, Italy). Both vaccines are approved for use in persons 10 through 25 years of age. MenB-FHbp is licensed as a 2- or 3-dose series, and MenB-4C is licensed as a 2-dose series for all groups. Either vaccine is recommended for routine use in persons 10 years and older who are at increased risk of serogroup B meningococcal disease (category A recommendation)...
September 2016: Pediatrics
https://www.readbyqxmd.com/read/27515662/saliva-of-rhipicephalus-boophilus-microplus-acari-ixodidae-inhibits-classical-and-alternative-complement-pathways
#10
Naylene C S Silva, Vladimir F Vale, Paula F Franco, Nelder F Gontijo, Jesus G Valenzuela, Marcos H Pereira, Mauricio R V Sant'Anna, Daniel S Rodrigues, Walter S Lima, Blima Fux, Ricardo N Araujo
BACKGROUND: Rhipicephalus (Boophilus) microplus is the main ectoparasite affecting livestock worldwide. For a successful parasitism, ticks need to evade several immune responses of their hosts, including the activation of the complement system. In spite of the importance of R. microplus, previous work only identified one salivary molecule that blocks the complement system. The current study describes complement inhibitory activities induced by R. microplus salivary components and mechanisms elicited by putative salivary proteins on both classical and alternative complement pathways...
2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27495980/strong-predictive-value-of-mannose-binding-lectin-levels-for-cardiovascular-risk-of-hemodialysis-patients
#11
Felix Poppelaars, Mariana Gaya da Costa, Stefan P Berger, Solmaz Assa, Anita H Meter-Arkema, Mohamed R Daha, Willem J van Son, Casper F M Franssen, Marc A J Seelen
BACKGROUND: Hemodialysis patients have higher rates of cardiovascular morbidity and mortality compared to the general population. Mannose-binding lectin (MBL) plays an important role in the development of cardiovascular disease. In addition, hemodialysis alters MBL concentration and functional activity. The present study determines the predictive value of MBL levels for future cardiac events (C-event), cardiovascular events (CV-event) and all-cause mortality in HD patients. METHODS: We conducted a prospective study of 107 patients on maintenance hemodialysis...
2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27389986/genes-regulated-by-potassium-channel-tetramerization-domain-containing-15-kctd15-in-the-developing-neural-crest
#12
Thomas C B Wong, Martha Rebbert, Chengdong Wang, Xiongfong Chen, Alison Heffer, Valeria E Zarelli, Igor B Dawid, Hui Zhao
Neural crest (NC) development is controlled precisely by a regulatory network with multiple signaling pathways and the involvement of many genes. The integration and coordination of these factors are still incompletely understood. Overexpression of Wnt3a and the BMP antagonist Chordin in animal cap cells from Xenopus blastulae induces a large number of NC specific genes. We previously suggested that Potassium Channel Tetramerization Domain containing 15 (Kctd15) regulates NC formation by affecting Wnt signaling and the activity of transcription factor AP-2...
2016: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/27377710/the-collectins-cl-l1-cl-k1-and-cl-p1-and-their-roles-in-complement-and-innate-immunity
#13
REVIEW
Soren W K Hansen, Katsuki Ohtani, Nitai Roy, Nobutaka Wakamiya
Both the complement system and collectins play important roles in our innate immune system. The collectins, which are characterized by their inclusion of a collagen-like region and a calcium-dependent carbohydrate recognition domain, are pattern recognition molecules and include the well characterized proteins mannan-binding lectin (MBL) and the surfactant proteins SP-A/-D. Collectin liver 1 (CL-L1), collectin kidney 1 (CL-K1) and collectin placenta 1 (CL-P1) are the most recently discovered collectins. Although their function is still under investigation, accumulating information suggests that CL-L1, CL-K1 and CL-P1 play important roles in host defense by recognizing a variety of microorganisms and interacting with effector proteins, including complement components...
October 2016: Immunobiology
https://www.readbyqxmd.com/read/27338768/interferon-%C3%AE-enhanced-clearance-of-group-a-streptococcus-despite-neutropenia
#14
Satoshi Uchiyama, Nadia Keller, Erika Schlaepfer, Christina Grube, Reto A Schuepbach, Roberto F Speck, Annelies S Zinkernagel
BACKGROUND: Neutrophils and monocytes are crucial for controlling bacterial infections. More-frequent bacterial infections are accordingly encountered in neutropenic patients undergoing chemotherapy. This is not the case for pegylated interferon α (IFN-α)-induced neutropenia. We hypothesized that IFN-α induces a compensatory innate antibacterial state that prevents bacterial infections despite the neutropenia. METHODS: To investigate whether patients with hepatitis C virus infection treated with IFN-α killed group A Streptococcus (GAS) better than before initiating therapy, whole blood was used to perform ex vivo GAS killing assays before, during, and after IFN-α therapy...
July 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27307559/an-inhibitor-of-the-alternative-pathway-of-complement-in-saliva-of-new-world-anopheline-mosquitoes
#15
Antonio F Mendes-Sousa, Daniel C Queiroz, Vladimir F Vale, José M C Ribeiro, Jesus G Valenzuela, Nelder F Gontijo, John F Andersen
The complement system present in circulating blood is an effective mechanism of host defense, responsible for the killing of pathogens and the production of potent anaphylatoxins. Inhibitors of the complement system have been described in the saliva of hematophagous arthropods that are involved in the protection of digestive tissues against complement system-mediated damage. In this study, we describe albicin, a novel inhibitor of the alternative pathway of complement from the salivary glands of the malaria vector, Anopheles albimanus The inhibitor was purified from salivary gland homogenates by reverse-phase HPLC and identified by mass spectrometry as a small (13...
July 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27235854/experimentally-induced-anti-myeloperoxidase-vasculitis-does-not-require-properdin-masp-2-or-bone-marrow-derived-c5
#16
Simon J Freeley, Reena J Popat, Kiran Parmar, Martin Kolev, Beverley J Hunt, Cordula M Stover, Willhelm Schwaeble, Claudia Kemper, Michael G Robson
Anti-neutrophil cytoplasmic antibody vasculitis is a systemic autoimmune disease with glomerulonephritis and pulmonary haemorrhage as major clinical manifestations. The name reflects the presence of autoantibodies to myeloperoxidase and proteinase-3, which bind to both neutrophils and monocytes. Evidence of the pathogenicity of these autoantibodies is provided by the observation that injection of anti-myeloperoxidase antibodies into mice causes a pauci-immune focal segmental necrotizing glomerulonephritis which is histologically similar to the changes seen on renal biopsy in patients...
September 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27183616/properdin-mediated-c5a-production-enhances-stable-binding-of-platelets-to-granulocytes-in-human-whole-blood
#17
Adam Z Blatt, Gurpanna Saggu, Koustubh V Kulkarni, Claudio Cortes, Joshua M Thurman, Daniel Ricklin, John D Lambris, Jesus G Valenzuela, Viviana P Ferreira
Enhanced levels of platelet/granulocyte aggregates (PGAs) are found in patients suffering from many different inflammatory vascular diseases, and their formation in animal models of vascular disease is associated with increased thromboinflammation and worsened outcomes. The complement system, a part of the innate immune system, influences PGA formation, but the mechanisms for its effects are unknown. In this study, we have defined complement-mediated mechanisms that enhance PGA formation in human whole blood stimulated with thrombin receptor-activating peptide (TRAP) using ex vivo flow cytometry assays...
June 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27153925/phospholipase-a2-receptor-related-membranous-nephropathy-and-mannan-binding-lectin-deficiency
#18
Stéphane Bally, Hanna Debiec, Denise Ponard, Frédérique Dijoud, John Rendu, Julien Fauré, Pierre Ronco, Chantal Dumestre-Perard
Most patients with idiopathic membranous nephropathy (IMN) have IgG4 autoantibodies against phospholipase A2 receptor (PLA2R). C3 and C5b-9 are found in immune deposits of IMN kidney biopsy specimens, but the pathway of complement activation in IMN remains elusive. We report the case of a patient who developed IMN with intense staining for PLA2R, IgG4, C3, C5b-9, factor B, and properdin and very weak staining for C1q, C4d, and IgG1. Measurement of mannan binding lectin (MBL) antigenic level and activity revealed MBL deficiency...
December 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27148258/netosing-neutrophils-activate-complement-both-on-their-own-nets-and-bacteria-via-alternative-and-non-alternative-pathways
#19
Joshua Yuen, Fred G Pluthero, David N Douda, Magdalena Riedl, Ahmed Cherry, Marina Ulanova, Walter H A Kahr, Nades Palaniyar, Christoph Licht
Neutrophils deposit antimicrobial proteins, such as myeloperoxidase and proteases on chromatin, which they release as neutrophil extracellular traps (NETs). Neutrophils also carry key components of the complement alternative pathway (AP) such as properdin or complement factor P (CFP), complement factor B (CFB), and C3. However, the contribution of these complement components and complement activation during NET formation in the presence and absence of bacteria is poorly understood. We studied complement activation on NETs and a Gram-negative opportunistic bacterial pathogen Pseudomonas aeruginosa (PA01, PAKwt, and PAKgfp)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27146825/testing-the-activity-of-complement-convertases-in-serum-plasma-for-diagnosis-of-c4nef-mediated-c3-glomerulonephritis
#20
Anna M Blom, Fernando Corvillo, Michal Magda, Grzegorz Stasiłojć, Pilar Nozal, Miguel Ángel Pérez-Valdivia, Virginia Cabello-Chaves, Santiago Rodríguez de Córdoba, Margarita López-Trascasa, Marcin Okrój
Autoantibodies termed C3-nephritic factor (C3NeF), which stabilize convertases of the alternative complement pathway, often stimulate autoinflammatory diseases. However, knowledge about analogous autoantibodies acting on the classical pathway (C4NeF) is limited to a few reports, which indicate association with kidney dysfunction, systemic lupus erythematous, and infections. C4NeF may appear independently from C3NeF, but the lack of a routine diagnostic method predisposes C4NeF for being an underestimated player in autoinflammatory episodes...
July 2016: Journal of Clinical Immunology
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